title: Vitamin E suppresses enhancement of factor VIII-dependent thrombin generation by systemic hypoxia.
abstract: OBJECTIVE
  Increased thrombin activity is an essential component of hemostatic reactions. This study elucidates how various hypoxic interventions impact endogenous thrombin generation (TG) after treatment with/without lipophilic antioxidant vitamin E.
  
  
  METHODS
  Twenty-four healthy sedentary men were randomly assigned to vitamin E (n=12) and placebo (n=12) groups. These subjects were randomly exposed to 12% (severe hypoxia), 15% (moderate hypoxia), 18% (light hypoxia), and 21% (normoxia) O(2) for 2 hours in a normobaric hypoxia chamber. A novel calibrated, automated thrombinography approach was used to measure TG in plasma.
  
  
  RESULTS
  In the placebo group, severe hypoxia enhanced plasma FVIII level/activity and TG, which was accompanied by increased urinary 15-F2t-8-isoprostane level and decreased plasma total antioxidant content and superoxide dismutase activity. However, depletion of FVIII by incubation with anti-FVIII antibodies in plasma suppressed enhancement of TG by severe hypoxia. After administration of 1000 IU vitamin E, severe hypoxia did not significantly alter urinary 15-F(2t)-8-isoprostane level and plasma total antioxidant content, superoxide dismutase activity, FVIII level/activity, or TG. Moreover, redox status, FVIII level/activity, and TG were constant in response to moderate hypoxia, light hypoxia, and normoxia in the placebo and vitamin E groups.
  
  
  CONCLUSIONS
  We conclude that severe hypoxia promotes FVIII-dependent TG, likely by elevating oxidative stress; this hypoxic effect was ameliorated by pretreatment with vitamin E.
authors.affiliation: Graduate Institute of Rehabilitation Science, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan. s5492@mail.cgu.edu.tw
authors.forename: Jong-Shyan
authors.initials: JS
authors.lastname: Wang
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Cheng
authors.forename: Hsiu-Chuan
authors.initials: HC
authors.lastname: Yen
authors.forename: Bih-Show
authors.initials: BS
authors.lastname: Lou
authors.forename: Huang-Chun
authors.initials: HC
authors.lastname: Liu
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D005169:Factor VIII / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D028421:Isoprostanes / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013917:Thrombin / Q000096:biosynthesis*; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D028421:Isoprostanes; D014810:Vitamin E; D005169:Factor VIII; D003404:Creatinine; D013482:Superoxide Dismutase; D013917:Thrombin